A Study of Selexipag as Add-On Treatment to Standard of Care in Children With Pulmonary Arterial Hypertension
- Conditions
- Hypertension, Pulmonary
- Interventions
- Drug: Placebo
- Registration Number
- NCT04175600
- Lead Sponsor
- Actelion
- Brief Summary
The purpose of this study is to evaluate whether the addition of selexipag to standard of care treatment delays disease progression in children with Pulmonary Arterial Hypertension (PAH) in comparison to placebo.
- Detailed Description
Pediatric PAH is a rare and progressive disorder associated with considerable morbidity and mortality. Given the significant medical need to develop treatments in children with PAH, further clinical studies in the pediatric population are therefore needed to provide more data for the management of PAH in children. Selexipag (JNJ-67896049) is an orally available, selective, and long-acting non-prostanoid agonist of the prostacyclin receptor approved and commercially available for the treatment of adult participants with PAH. Selexipag and its metabolite possess anti-fibrotic, anti-proliferative, and anti-thrombotic properties. Currently, no medicines targeting prostacyclin pathway are approved for pediatric use in PAH. An effective and orally available therapy acting on the prostacyclin receptor such as selexipag introduced at medically appropriate stage of PAH disease, and primarily in combination with current first-line oral PAH-specific medicines in participants in need of additional therapy because of insufficient disease control would represents a major advance to the therapeutic management of PAH pediatric participants. This study consists of a screening period of up to 6 weeks and a double-blind treatment period, including up-titration and maintenance periods, followed by a 3-year open-label extension period (OLEP) and a 30-day safety follow-up period that occurs after the last dose of study intervention (either double-blind or open-label). Safety, pharmacokinetic and efficacy assessments will be performed during the study. An Independent Data Monitoring Committee (IDMC) will be established to monitor data on an ongoing basis, to review interim data, and to ensure the continuing safety of the participants enrolled in this study. The approximate duration of the study is 8 years.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 138
- Participants between greater than or equal to (>=) 2 and less than (<) 18 years of age weighing >=9 kilogram (kg) at randomization
- Pulmonary arterial hypertension (PAH) diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before participant's screening
- PAH (World Health Organization [WHO] Group 1), including participants with Down syndrome, of the following etiologies: Idiopathic PAH (IPAH); Heritable PAH (HPAH); PAH associated with congenital heart disease (PAH-associated with congenital heart disease [aCHD]) (PAH with coincidental CHD [that is, a small atrial septal defect, ventricular septal defect, or patent ductus arteriosus that does not itself account for the development of elevated PVR] and if approved by the BCAC) and Post-operative PAH (persisting / recurring/ developing >=6 months after repair of CHD); Drug or toxin-induced; PAH associated with Human immunodeficiency virus (HIV)
- WHO functional class (FC) II and III
- Participants treated with at least 1 PAH-specific treatment, example, an Endothelin receptor antagonist (ERA) and/or a Phosphodiesterase type-5 (PDE-5) inhibitor/soluble guanylate cyclase stimulator, provided that the treatment dose(s) has been stable for at least 3 months prior to first dose of study intervention
- PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease, and/or pulmonary capillary hemangiomatosis
- PAH associated with Eisenmenger syndrome
- Previous exposure to Uptravi (selexipag)
- Known concomitant life-threatening disease with a life expectancy <12 months
- Pregnant, planning to become pregnant, or lactating
- Known allergies, hypersensitivity, or intolerance to selexipag or its excipients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Selexipag Selexipag Participants will receive selexipag based on the body weight on Day 1 and will continue thereafter with twice daily dosing. Selexipag will be uptitrated during the first 12 weeks until the participants reaches the individual maximum tolerated dose (iMTD) or until a maximum dose corresponding to their baseline body-weight category is achieved. Uptitration is followed by a maintenance period after Week 12 until end of treatment (EOT), at the maximum tolerated dose. Placebo Placebo Participants will receive matching placebo based on the body weight on Day 1 and will continue thereafter with twice daily dosing.
- Primary Outcome Measures
Name Time Method Time to Disease Progression From randomization up to 7 days after study treatment discontinuation (up to 5 years) Time to disease progression is the time from randomization up to 7 days after study treatment discontinuation. Disease progression is defined as the first occurrence of either of the following components: Death (all causes), Atrial septostomy or Potts' anastomosis, or registration on lung transplant list, Hospitalization due to worsening pulmonary arterial hypertension (PAH), Clinical worsening of PAH.
- Secondary Outcome Measures
Name Time Method Change from Baseline in Systolic and Diastolic Arterial Blood Pressure Baseline up to end of treatment (EOT) (up to 8 years) Change from baseline in systolic and diastolic arterial blood pressure to all assessed time points will be reported.
Change from Baseline in Pulse Rate Baseline up to EOT (up to 8 years) Change from baseline in pulse rate to all assessed time points will be reported.
Change from Baseline in Body Weight Baseline up to EOT (up to 8 years) Change from baseline in body weight to all assessed time points will be reported.
Change from Baseline in Height Baseline up to EOT (up to 8 years) Change from baseline in height to all assessed time points will be reported.
Sexual Maturation (Tanner Stage) Change from Baseline to all Assessed Time Points Up to 3 days after study treatment discontinuation (up to EOT) (multiple timepoints up to 8 years) The sexual maturation change as per Tanner stage will be assessed from baseline to all assessed time points. Tanner stage I is defined as no pubic hair at all (prepubertal Dominic state); stage II is defined as a small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females); stage III is defined as when the hair becomes more coarse and curly, and begins to extend laterally; stage IV is defined as adult-like hair quality, extending across pubis but sparing medial thighs; and stage V is defined as when the: hair extends to medial surface of the thighs.
Percentage of Participants with Treatment-emergent Marked Laboratory Abnormalities Baseline up to EOT (up to 8 years) Percentage of participants with treatment-emergent marked laboratory (serum chemistry \[including pregnancy testing and thyroid markers\] and hematology) abnormalities will be reported.
Treatment-emergent Change from Baseline in Thyroid Stimulating Hormone Baseline up to EOT (up to 8 years) Treatment-emergent change from baseline in thyroid stimulating hormone over time will be reported.
Time to First Clinical Event Committee (CEC)-confirmed Hospitalization or Death for PAH Until 7 days after study treatment discontinuation (Up to 8 years) Time to first CEC-confirmed hospitalization or death for PAH is the time (days) from randomization to first occurrence of CEC-confirmed hospitalization for PAH or death due to PAH up to 7 days after study intervention discontinuation.
Trough Plasma Concentration at Steady-state (Ctrough,ss) of Selexipag and its Metabolite ACT-333679 Weeks 16, 24 and every 12 weeks thereafter (up to 8 years) Ctrough,ss is defined as the plasma concentration just prior to the morning dose, with the last study intervention administration one day prior to the pharmacokinetic sampling and will be reported for Selexipag and its metabolite ACT-333679.
Change from Baseline at Week 24 in Log2 N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Baseline up to Week 24 The change from baseline at week 24 in log2 NT-proBNP will be reported.
Percentage of Participants with Treatment-emergent Electrocardiogram Abnormalities Baseline up to EOT (up to 8 years) Percentage of participants with treatment-emergent electrocardiogram abnormalities will be reported.
Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious AEs Up to 5 years An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are AEs with onset during the intervention period or that are a consequence of a pre-existing condition that has worsened since baseline. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Percentage of Participants with AEs Leading to Premature Discontinuation of Study Treatment Up to 5 years Percentage of participants with AEs leading to premature discontinuation of study treatment will be reported.
Trial Locations
- Locations (114)
Szpital Kliniczny im Karola Jonschera
🇵🇱Poznan, Poland
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
UCSF
🇺🇸San Francisco, California, United States
Childrens Hospital Colorado
🇺🇸Aurora, Colorado, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Congenital Heart Center of the University of Florida
🇺🇸Gainesville, Florida, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Detroit Medical Center
🇺🇸Detroit, Michigan, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Childrens Hospital Of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
University of Virginia Division of Pediatric Cardiology
🇺🇸Charlottesville, Virginia, United States
Queensland CHILDREN'S HOSPITAL
🇦🇺South Brisbane, Australia
State Institution Republican Scientific And Practical Center For Pediatric Surgery
🇧🇾Minsk, Belarus
Health Institution 4Th City Children'S Clinical Hospital
🇧🇾Minsk, Belarus
ULB Hôpital Erasme
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Universitaire Ziekenhuizen Leuven
🇧🇪Leuven, Belgium
Complexo de Prevencao,Diagnostico,Terapia e Reabilitacao Respiratoria LTDA Hospital Dia do Pulmao
🇧🇷Blumenau, Brazil
Fundacao Universitaria de Cardiologia - Instituto de Cardiologia e Transplantes do DF
🇧🇷Brasilia, Brazil
Hospital Pequeno Principe
🇧🇷Curitiba, Brazil
Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes
🇧🇷Fortaleza, Brazil
Irmandade Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Brazil
Fundacao Universitaria de Cardiologia
🇧🇷Porto Alegre, Brazil
Irmandade Santa Casa de Misericordia de Sao Paulo
🇧🇷Sao Paulo, Brazil
SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
🇧🇷Sao Paulo, Brazil
Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead
🇧🇬Sofia, Bulgaria
Stollery Children's Hospital
🇨🇦Edmonton, Alberta, Canada
Hospital For Sick Children
🇨🇦Toronto, Ontario, Canada
Beijing Anzhen Hospital
🇨🇳Beijing, China
Guangzhou Women And Children's Medical Center
🇨🇳Guangzhou, China
Qingdao Women and Children's Hospital
🇨🇳Qingdao, China
Shanghai Childrens Medical Center
🇨🇳Shanghai, China
Children's Hospital of Fudan University
🇨🇳Shanghai, China
The General Hospital of Northern Theater Command
🇨🇳Shenyang, China
Clinica San Rafael
🇨🇴Bogota, Colombia
Fundacion Neumologica Colombiana
🇨🇴Bogota, Colombia
Fundacion Santa Fe de Bogota
🇨🇴Bogota, Colombia
Clínica Imbanaco S.A.S.
🇨🇴Cali, Colombia
Fundacion Cardiovascular de Colombia
🇨🇴Piedecuesta, Colombia
Hospital Universidad del Norte
🇨🇴Soledad, Colombia
New Children's Hospital of the Helsinki University Hospital (HUS)
🇫🇮Helsinki, Finland
Hôpital Cardiologique - Chru Lille
🇫🇷Lille Cedex, France
Hopital de la Timone
🇫🇷Marseille Cedex 5, France
CHU Arnaud de Villeneuve
🇫🇷Montpellier Cedex 5, France
Hôpital Necker - Enfants Malades
🇫🇷Paris, France
Hôpital Cardiologique Du Haut-Lévêque
🇫🇷Pessac, France
Chu Hopital Des Enfants
🇫🇷Toulouse Cedex 9, France
Universitätsklinikum Freiburg Zentrum
🇩🇪Freiburg, Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Herzzentrum Leipzig GmbH
🇩🇪Leipzig, Germany
Klinikum der Universitaet Muenchen
🇩🇪München, Germany
Gottsegen György Országos Kardiológiai Intézet
🇭🇺Budapest, Hungary
Our Lady's Children's Hospital
🇮🇪Dublin, Ireland
Rambam Medical Center
🇮🇱Haifa, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Azienda Ospedaliera Policlinico S. Orsola-Malpighi
🇮🇹Bologna, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Universta Degli Studi Di Padova
🇮🇹Padova, Italy
Ospedale Pediatrico Bambin Gesù
🇮🇹Roma, Italy
IRCCS Policlinico San Donato
🇮🇹S. Donato Milanese, Italy
AOU Città della Salute e della Scienza di Torino, Presidio Ospedale Infantile Regina Margherita
🇮🇹Torino, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Pusan National University Yangsan Hospital
🇰🇷Yangsan-si, Korea, Republic of
Vilnius University Hospital Santariskiu Clinics
🇱🇹Vilnius, Lithuania
National Heart Institute
🇲🇾Kuala Lumpur, Malaysia
CICUM San Miguel
🇲🇽Guadalajara, Mexico
Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas
🇲🇽Mexico, Mexico
Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
🇲🇽Monterrey, Mexico
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Uniwersytecki Szpital Dzieciecy w Krakowie
🇵🇱Krakow, Poland
Instytut Pomnik Centrum Zdrowia Dziecka
🇵🇱Warszawa, Poland
Wojewodzki Szpital Specjalistyczny we Wroclawiu
🇵🇱Wroclaw, Poland
Slaskie Centrum Chorob Serca
🇵🇱Zabrze, Poland
Uls Sao Jose - Hosp. Santa Marta
🇵🇹Lisboa, Portugal
Uls Sao Joao - Hosp. Sao Joao
🇵🇹Porto, Portugal
Kazan State Medical University
🇷🇺Kazan, Russian Federation
Cardiovascular Pathology Research Institute of Siberian Branch of RAMS
🇷🇺Kemerovo, Russian Federation
Childrens City Clinical Hospital n.a. Bashlyaeva
🇷🇺Moscow, Russian Federation
Veltischev Research and Clinical Institute for Pediatrics of the Pirogov RNRMU
🇷🇺Moscow, Russian Federation
Samara Regional Clinical Cardiological Dispensary
🇷🇺Samara, Russian Federation
Univerzitetska Dečja Klinika
🇷🇸Belgrade, Serbia
Hosp Univ A Coruna
🇪🇸A Coruña, Spain
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Hosp. Sant Joan de Deu
🇪🇸Esplugues de Llobregat, Spain
Hosp. Gral. Univ. Gregorio Maranon
🇪🇸Madrid, Spain
Hosp. Univ. La Paz
🇪🇸Madrid, Spain
Hosp. Virgen Del Rocio
🇪🇸Sevilla, Spain
Drottning Silvias barn- och ungdomssjukhus
🇸🇪Gothenburg, Sweden
Skanes universitetssjukhus
🇸🇪Lund, Sweden
Centre Hospitalier Universitaire Vaudois CHUV
🇨🇭Lausanne, Switzerland
Kaohsiung Veterans General Hospital
🇨🇳Kaohsiung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Chiang Mai University Hospital
🇹🇭Chiang Mai, Thailand
Songklanagarind hospital
🇹🇭Songkhla, Thailand
Cukurova Balcali Hospital Application and Research Center
🇹🇷Adana, Turkey
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
CAPA Istanbul University Medical Faculty
🇹🇷Istanbul, Turkey
Mehmet Akif Ersoy Training and Research Hospital
🇹🇷Istanbul, Turkey
Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital
🇹🇷Izmir, Turkey
Izmir Tepecik Training and Research Hospital
🇹🇷Izmir, Turkey
Dnipropetrovsk clinical medical center of Mother and Child after prof. Rudnev
🇺🇦Dnipro, Ukraine
MI 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery'
🇺🇦Dnipro, Ukraine
Scientific Practical Medical Center for Pediatric Cardiology and Cardio Surgery of the MOH
🇺🇦Kyiv, Ukraine
MI Zaporizhzhia Regional Clinical Childrens Hospital of Zaporizhzhia Regional Council
🇺🇦Zaporizhzhya, Ukraine
Hanoi Medical University Hospital
🇻🇳Hanoi, Vietnam
Tam Anh Hospital
🇻🇳Ho Chi Minh, Vietnam
University Medical Center Ho Chi Minh city
🇻🇳Ho Chi Minh, Vietnam
Children's Hospital 1
🇻🇳Ho Chi Minh, Vietnam